Successful aging involves not only the maintenance of cognitive function, but sustained normal physical function. One measure of abnormal physical function is abnormal gait and balance (impaired mobility), an important outcome in geriatric epidemiology. Impaired mobility is associated with falls, institutionalization, incident stroke, and mortality. Some conventional vascular disease risk factors (such as physical inactivity, dyslipidemia) have been associated with impaired mobility, though less has been demonstrated regarding emerging vascular risk factors, such as inflammatory biomarkers. Serial measures of vascular disease risk factors, such as decline in physical activity, have not been used in studies examining risk of impaired mobility. Few studies on impaired mobility have included Hispanics. Subclinical neurovascular disease, defined as white matter hyperintensities and silent brain infarcts seen on magnetic resonance imaging (MRI), is associated with vascular disease risk factors and has been linked to impaired mobility. There have been few studies examining the pathway by which all three (vascular risk factors, subclinical neurovascular disease and impaired mobility) may be linked. This K23 proposal will take advantage of the existing infrastructure in the Northern Manhattan Study (NOMAS), a well respected epidemiological study with a high proportion of Hispanics aimed at elucidating risk factors for vascular outcomes (stroke, myocardial infarction, vascular death). Mobility examinations will be performed on participants in the MRI sub-study who have been returning for a 5 year neuro-psychological evaluation. Our aim is to characterize the association between vascular disease risk factors (physical inactivity, dyslipidemia, inflammatory biomarkers) with measures of mobility (gait speed and Tinetti gait and balance scale as the primary outcomes). We will analyze whether these associations remain after including global and regional (frontal lobe versus peri-ventricular for example) measures of white matter hyperintensities and silent brain infarction is acting as mediators. In order to achieve these scientific goals I will need training in three areas: selected topics in geriatric medicine, gait and balance measures in the geriatric population, and advanced statistical and epidemiological methods. Achieving these scientific and training goals will allow me to transition into being an independently funded academic neurologist with a focus on the contributions of subclinical stroke to unsuccessful aging, as well as broaden my expertise on stroke in the geriatric population. PUBLIC HEALTH RELEVANCE: Successful aging involves not only the maintenance of cognitive function, but also sustained normal physical function, of which mobility is a critical component. Multiple silent strokes to the brain may impair mobility in the elderly. The goal of this project is to better understand the role of vascular disease on impaired mobility so as to derive treatment interventions.